Novel benzylimidazole derivatives

ABSTRACT

Novel benzylimidazole derivatives of the formula: ##STR1## wherein X is halogen, nitro, alkyl, alkoxy, or halobenzyloxy; 
     m is an integer of 0 to 3; 
     Y is oxa, thia or substituted- or unsubstituted-imino; 
     R 1  is alkyl, dialkylaminoalkyl, dibenzylaminoalkyl, 1-pyrrolidinyl, 2-imidazolin-2-yl, or a group of --(CH 2 )n--Z--Q 
     (wherein 
     n is an integer of 0 to 4; 
     Z is oxa, thia, or a single bond; and 
     Q is substituted- or unsubstituted-phenyl or thienyl) ##STR2## is methylene, 1-(1-imidazolyl)-1-methylmethylene, 1-(1-imidazolyl)-1-phenylmethylene, 1-phenylmethylene, or substituted or unsubstituted alkylidene; 
     the benzene ring of the above formula being optionally condensed with another benzene ring 
     with the proviso that when ##STR3## is methylene said benzene ring is condensed with another benzene ring, and acid addition salts thereof which are useful as an antimycotic drug or agricultural fungicide.

I. SUMMARY OF THE INVENTION

This invention relates to novel benzylimidazole derivatives useful as anantimycotic drug or agricultural fungicide. Such compounds are, forexample, disclosed in Japanese Unexamined Patent Publication No.50-148357 and the European Journal of Medicinal Chemistry 14, No. 3, pp227-230, 231-237, 243-245 (1979). But the compounds of the followingformula (I) are novel. ##STR4## , wherein X is halogen, nitro, C₁ to C₅alkyl, C₁ to C₅ alkoxy or halo-benzyloxy;

m is an integer of 0 to 3;

Y is oxa, thia or imino optionally substituted by C₁ to C₅ alkanoyl, C₁to C₅ halo-alkanoyl or C₁ to C₅ alkyl;

R¹ is C₁ to C₅ alkyl, C₃ to C₁₀ dialkylaminoalkyl, C₁₅ to C₂₀dibenzylaminoalkyl, 1-pyrrolidinyl, 2-imidazolin-2-yl, or a group of--(CH₂)n--Z--Q

(wherein

n is an integer of 0 to 4;

Z is oxa, thia, or a single bond;

Q is phenyl or thienyl optionally substituted by 1 to 3 members selectedfrom halogen, nitro, C₁ to C₅ alkyl, and C₁ to C₅ alkoxy); ##STR5## ismethylene, 1-(1-imidazolyl)-1-methylmethylene,1-(1-imidazolyl)-1-phenylmethylene, 1-phenylmethylene, or C₁ to C₅alkylidene optionally substituted by phenyl;

the benzene ring of the above formula being optionally condensed withanother benzene ring

with the proviso that when ##STR6## is methylene said benzene ring iscondensed with another benzene ring, and pharmaceutically acceptableacid addition salts thereof.

II. Detailed Explanation

In the above general formula, halogen means chloro, bromo, fluoro andiodo, preferably chloro. C₁ and C₅ Alkyl means methyl, ethyl, propyl,isopropyl, butyl, sec-butyl, pentyl, isopentyl, and the like and C₁ toC₅ alkoxy means methoxy, ethoxy, propoxy, isopropoxy, butyloxy,sec-butyloxy, pentyloxy, isopentyloxy, and the like. C₁ to C₅ Alkanoylmeans formyl, acetyl, propionyl, butyryl, and the like. C₃ to C₁₀Dialkylaminoalkyl means dimethylaminoethyl, diethylaminoethyl,dipropylaminobutyl, methylethylaminoethyl, and the like. C₁ to C₅Alkylidene means methylene, ethylidene, propylidene, isopropylidene,butylidene, pentylidene, and the like.

Compounds (I) can be easily converted to the correspondingpharmaceutically acceptable acid addition salts, which are includedwithin the scope of this invention. Representative acids which can formthe pharmaceutically acceptable salts are organic acids such as aceticacid, citric acid, tartaric acid, methanesulfonic acid, malic acid,succinic acid, oxalic acid, salicyclic acid, or the like and inorganicacids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitricacid, phosphoric acid, or the like.

III. Preparation

Compounds (I) may be prepared according to the following scheme:##STR7## (wherein M is hydrogen or alkali metal;

A is halogen or an ester residue;

B and D each is hydrogen or alkyl;

and X, m, Y, R¹, R² and R³ each has the same significance as givenearlier)

(First Step)

This process may be carried out by reacting Compound (II) with Compound(III) in the presence of a base in an inert solvent at room temperatureor under heating. Representative bases are sodium hydroxide, potassiumhydroxide, sodium hydride, sodium amide, potassium amide, sodiumethoxide, potassium carbonate, and the like. Representative inertsolvents are dimethylformamide, benzene, methanol, chloroform, dioxane,tetrahydrofuran, acetone, and the like.

The starting compound (II) is available, for example, by treating theketone (IV) with N,N'-thionyldiimidazole or N,N'-carbonyldiimidazole forimidazole formation. The reaction is carried out in an inert solventsuch as methylene chloride, chloroform, tetrahydrofuran, dioxane,benzene, acetonitrile, or 1,2-dichloroethane at room temperature orunder cooling.

(Second Step)

The reaction of the starting compound (IV) with the compound (III) maybe carried out in the same manner as in the First Step. Then theintermediate (V) is subjected to the imidazole formation in the samemanner as in the above preparation of the starting compound (II).

IV. Effect

Compounds (I) and the pharmaceutically acceptable salts thereof preparedin this invention exhibit excellent antimycotic activities and areuseful as an antimycotic drug for humans and animals.

Minimum Inhibitory Concentration (MIC, μ/ml) in vitro of some typicalCompounds (I) are indicated in the following Table 1. The compoundnumbers correspond to the structure of the products prepared in therespective numbered Examples.

                  TABLE 1                                                         ______________________________________                                        MIC Values (γ/ml)                                                               Fungi                                                                 Compound  Aspergillus                                                                              Candida     Trichophyton                                 No.       fumigates  albicans M-9                                                                              asteroides                                   ______________________________________                                        1         3.1        6.2         <0.1                                         7         1.6        100.0       <0.1                                         8         1.6        25.0        50.0                                         13        1.6        6.2         <0.1                                         17        3.1        3.1         <0.1                                         22        1.6        6.2         <0.1                                         28        6.2        12.5        <0.1                                         34        6.2        50.0        1.6                                          39        0.4        6.2         <0.1                                         40        12.5       25          1.6                                          41        6.2        3.1         <0.1                                         42        3.1        12.5        3.1                                          43        1.6        12.5        3.1                                          44        3.1        12.5        3.1                                          45        6.2        25          3.1                                          46        6.2        25          3.1                                          47        6.2        12.5        1.6                                          62        0.8        25.0        <0.1                                         66        6.2        12.5        0.2                                          67        6.2        6.2         0.2                                          68        6.2        12.5        3.1                                          69        12.5       25          1.6                                          ______________________________________                                    

Compounds (I) and their acid addition salts exhibit excellent antifungalactivities against various phytopathogenic fungi and soil bornepathogens and are useful as agricultural fungicides.

1. Control Test to Botrytis rot(gray mold) of Cucumber

(1) Test Method

A seed of cucumber (cultivar:Matsukaze) was sown in a vinyl chloride-cupof 9 cm in diameter containing soil in a greenhouse and cultivated. Atthe primary leaf stage, 2.5 ml each of the solution containing aprescribed concentration of the test compound was applied over the abovecucumber, which was kept at 25° to 26° C. in 80% humidity for 24 hours.A suspension of Botrytis cinerea spores was inoculated onto the leavesat five spots per leaf and the leaves were kept at 80° C. in 95%humidity for 72 hours.

(2) Results

The results are shown by percent disease control (%) calculated from thediseased degree according to the following formula. ##EQU1##

The compounds numbered in the following Table 2 each have the samestructure as that of the compounds in the corresponding numberedExamples.

                  TABLE 2                                                         ______________________________________                                        Compd.  Concentration            Percent Disease                              No.     (ppm)       Diseased Degree                                                                            Control (%)                                  ______________________________________                                        1       500         0            100                                          3       "           "            "                                            6       "           "            "                                            7       "           40            60                                          8       "           0            100                                          15      "           "            "                                            17      "           "            "                                            24      "           "            "                                            27      "           "            "                                            34      "           "            "                                            61      "           "            "                                            62      "           "            "                                            un-                                                                           treated --          100           0                                           ______________________________________                                         (Note)-                                                                       Diseased degrees were calculated according to the subsequent             

    Disease condition                                                                              Marks    Numbers examined                                    ______________________________________                                        Largely faded lesions                                                         formed at inoculated                                                                           20       a                                                   parts                                                                         Back of the inoculated                                                        leaf faded       10       b                                                   Back of the inoculated                                                        leaf slightly faded                                                                            5        c                                                   No disease       0        d                                                   ______________________________________                                         ##STR8##                                                                 

2. Control Test to Anthracnose of Cucumber

(1) Test Method

A seed of cucumber (cultivar:Matsukaze) was sown on a vinyl chloride-cupof 9 cm in diameter in a greenhouse containing soil and cultivated. Atthe primary leaf stage, 2.5 ml each of the solution containing aprescribed concentration of the test compound was applied over the abovecucumber, which was kept at 25° to 26° C. in 80% humidity for 24 hours.A suspension of Colletotrichum lagenarium spores was inoculated onto theabove leaves at five spots per leaf and the leaves were kept at 25° C.in 95% humidity for 1 day and at 25° C. in 75 to 80% humidity for 6days.

(2) Results

Percent disease control (%) was calculated as mentioned in the abovetest 1.

                  TABLE 3                                                         ______________________________________                                        Compd.  Concentration            Percent Disease                              No.     (ppm)       Diseased Degree                                                                            Control (%)                                  ______________________________________                                        46      500         20           80                                           58      "           0            100                                          un-                                                                           treated --          100          0                                            ______________________________________                                    

3. Control Test to Powdery Mildew of Cucumber

(1) Test Method

A seed of cucumber (cultivar:Matsukaze) was sown in a vinyl chloride-cupof 9 cm in diameter containing soil in a greenhouse and cultivated. Atthe primary leaf stage, 5 ml each of a solution of the test compound ina prescribed concentration was applied over the above cucumber, whichwas kept at 25° to 26° C. for 1 day. Primary leaves of cucumberpreviously infected by pathogenic fungi of the powdery mildew(Shpaerotheca fuliginea) were taken and those having lesions coveredwith spores were cut out in 1 square centimeter pieces, which were stuckto the primary leaves in the cups for inoculation, four plots per leaf.The above treated leaves were kept at 25° to 26° C. for 10 days.

The spore formation on the inoculated plots was observed by amicroscope.

Standard of the evaluation:

(+): Formation of many spores and hypae observed on the inoculated plots

(-): Neither infected spots nor spore formation observed on theinoculated plots

(2) Results

    ______________________________________                                        Compd. No. Concentration (ppm)                                                                           Diseased Degree                                    ______________________________________                                         5         500             -                                                  21         "               -                                                  36         "               -                                                  78         "               -                                                  80         "               -                                                  untreated  --              +                                                  ______________________________________                                    

4. Control Test against rice plants blast

(1) Test Method

Seedlings of rice plant (cultivar:Aichi-asahi) reared in a greenhousefor 10 days were transplanted in a vinyl chloride-cup of 9 cm indiameter. A solution of the test compound at a prescribed concentrationwas applied to the above rice plants 14 days after the transplanting.One day after the application, a spore suspension of pathogenic fungi ofrice plant blast (Pyricularia oryzae) was sprayed on the leaf blades ofthe seedlings, which were kept at 28° C. in 98% humidity for 24 hoursand at 28° C. in 90% humidity for 7 days in a greenhouse. The number ofinfected spots on the inoculated leaves was observed.

(2) Results

The results are shown by percent disease control which was calculatedaccording to the following formula:

    ______________________________________                                        Percent Disease Control (%) =                                                  ##STR9##                                                                     Compd.  Concentration                                                                              Number of  Percent Disease                               No.     (ppm)        Spots      Control (%)                                   ______________________________________                                        23      500          271        89.5                                          28      "            45         98.3                                          36      "            25         99.0                                          78      "            99         96.2                                          un-                                                                           treated --           2589       0                                             ______________________________________                                    

V. How to Use

Compounds (I) or the salts thereof may be applied in a wide variety oforal or parenteral dosage forms solely or in admixture with additivessuch as diluents, carriers, dispersants and the like. The pharmaceuticalcompositions may be in the form of solutions, suspensions, powders,granules, tablets, injections, ointments, tinctures, and the like. Theformulations may be dispensed in a conventional manner. For example,Compounds (I) may be administered at a dose of 100 to 2000 mg per dayfor enteral application.

Further, compounds (I) and the salts thereof exhibit an excellentcontrol effect against the following phyto-pathogenic fungi and othersoil borne pathogens.

Rice plant: blast, damping-off, leaf spot

Wheat and barley: stem rust, loose smut, powdery mildew

Pear: red spot, scab, Alternaria leaf spot

Grape: gray rust, ripe rot, downy mildew, leaf spot, white rot, graymold, powdery mildew

Apple: Alternaria leaf spot, canker, black spot, red spot, blossomblight

Peach: brown rot

Cucumber: downy mildew, anthracnose, sclerotinia rot, gray mold, powderymildew

Green pepper: powdery mildew

Tobacco: brown spot, powdery mildew

Compounds (I) or the salts thereof may be formed into wettable powders,granules, powders, emulsions, tablets, aerosols, fumigations, oils, andthe like solely or in admixture with additives or carriers ordinarilyemployed in agricultural fungicides. Compounds (I) may be applied toplants at a dose of 0.5 to 100 g per are.

The following examples are provided to further illustrate thisinvention.

EXAMPLE 1 ##STR10## (step a)

To a solution of 60 g of imidazole in 300 ml of dry methylene chlorideis added 26.2 g of thionyl chloride, and the mixture is stirred at roomtemperature for 10 minutes, mixed with 20 g of Compound (1), and stirredat room temperature for 1.5 hours. The reaction mixture is mixed withice water and extracted with methylene chloride. The organic layer iswashed with water, dried over Glauber's salt, and concentrated. Theresidue is dissolved in a mixture of 5% methanol and methylene chlorideand chromatographed on a column of silica gel. The eluate isconcentrated and the residue is washed with a mixture of ethyl acetateand isopropyl ether to give 25.8 g of Compound (2).

mp. 150°-151° C.

IR: ν_(max) ^(Nujol) 3300-2100, 2570, 1630 cm⁻¹.

(step b)

To a solution of the sodium salt of Compound (2) prepared from 500 mg ofCompound (2), 164 mg of 60% sodium hydride and 5 ml of drydimethylformamide is added 828 mg of p-chlorobenzyl bromide, and themixture is stirred at room temperature for 15 minutes. The reactionmixture is mixed with ice water and extracted with methylene chloride.The organic layer is washed with water, dried over Glauber's salt, andconcentrated. The residue is chromatographed on a column of silica gel,which is eluted with a mixture of 2% methanol and methylene chloride.The eluate is collected and mixed with a mixture of hydrochloric acidand ethanol, and the mixture is concentrated. The residue iscrystallized from a mixture of ethyl acetate and ether andrecrystallized from a mixture of methanol and ethyl acetate to give 345mg of Compound (3) hydrochloride.

mp. 180.5°˜181° C. (decomposition)

IR: ν_(max) ^(Nujol) 2600 2300, 1649 cm⁻¹.

EXAMPLE 2 ##STR11##

To a solution of N,N'-thionyldiimidazole prepared from 2.95 g ofimidazole and 1.29 g of thionyl chloride in 15 ml of dry methylenechloride is added 2.0 g of Compound (4), and the mixture is extractedwith methylene chloride. The organic layer is washed with water, driedover Glauber's salt, and concentrated. The residue is chromatographed ona column of silica gel, which is eluted with methylene chloride torecover 750 mg of unreacted Compound (4). The eluate from 1%methanol-methylene chloride to 2% methanol-methylene chloride iscollected and concentrated, and the resulting residue is crystallizedfrom ethanolic hydrochloric acid and recrystallized from methanol-ethylacetate-ether to give 310 mg of Compound (5).

mp. 153°-163° C.

EXAMPLE 3 ##STR12##

To a solution of 1 g of Compound (2) in 5 ml of dimethylformamide isadded 322 mg of a 60% suspension of sodium hydride in mineral oil withice-cooling, and the mixture is stirred for 5 minutes, mixed with 1.14 gof methyliodide, and stirred at room temperature for 10 minutes. Thereaction mixture is diluted with ice water and extracted with ether. Theorganic layer is washed with water, dried over Glauber's salt, andconcentrated. The residue is chromatographed on a column of silica geland eluted with 37% methanol-methylene chloride. The eluate isconcentrated, and the residue is crystallized from hydrochloricacid-ethanol and recrystallized from methanol-acetic acid to give 520 mgof Compound (6).

mp. 190°-195° C.

Elemental Analysis (for C₁₂ H₁₂ ON₂.HCl): Calcd(%): C, 60.89; H, 5.54;N, 11.84; Cl, 14.98; Found(%): C, 60.78; H, 5.52; N, 11.73; Cl, 15.02.

EXAMPLES 4 TO 91

The following compounds are prepared in the same manner as mentioned inthe above Examples.

    __________________________________________________________________________     ##STR13##                                                                    Ex.                                                     mp (°C.)       No.                                                                              m X           Y    R.sup.1       R.sup.2                                                                            R.sup.3                                                                           Salt       or                    __________________________________________________________________________                                                            IR                    4  O --          2-O  CH.sub.3      CH.sub.3                                                                           Im  --         164-165               5  " "           "                                                                                   ##STR14##    Ph   Im  "          155-156               6  " "           "    C.sub.2 H.sub.5                                                                             CH.sub.2 HCl . 1/2H.sub.2 O                                                                       159-162               7  " "           "    n-C.sub.3 H.sub.7                                                                           "        "          146-148               8  " "           "    n-C.sub.4 H.sub.9                                                                           "        --         oily product                                                                  ν.sup. film                                                                1638                                                                          cm.sup.-1             9  " "           "    (CH.sub.2).sub.3N(CH.sub.3).sub.2                                                           "        1/4CH.sub.3 OH                                                                           oily product                                                                  ν.sup.film                                                                 1632                                                                          cm.sup.-1             10 " "           "    CH.sub.2 Ph   "        HCl        154-156               11 " "           "                                                                                   ##STR15##    "        --         85-86                 12 " "           "      "           "        HCl        180.5-181             13 " "           "                                                                                   ##STR16##    "        "          148.5-149             14 " "           "                                                                                   ##STR17##    "        "          161-163               15 " "           "                                                                                   ##STR18##    "        "          172-174               16 " "           "                                                                                   ##STR19##    "        --         94-94.5               17 " "           "                                                                                   ##STR20##    "        HCl        180-183               18 " "           "                                                                                   ##STR21##    "        "          138-147               19 " "           "                                                                                   ##STR22##    "        --         oily product                                                                  ν.sup.film                                                                 1639 cm.sup.-1        20 " "           "                                                                                   ##STR23##    "        "          oily product                                                                  ν.sup.film                                                                 1630 cm.sup.-1        21 " "           "                                                                                   ##STR24##    "        HCl        139-142               22 " "           "                                                                                   ##STR25##    "        "          165-172               23 " "           "    (CH.sub.2).sub.2 Ph                                                                         "        (COOH).sub.2                                                                             122.5-124.5           24 " "           "    (CH.sub.2).sub.2N(C.sub.2 H.sub.5).sub.2                                                    "        2(COOH).sub.2                                                                            80-81                 25 " "           "    (CH.sub.2).sub.2N(CH.sub.2 Ph).sub.2                                                        "        --         oily product                                                                  ν.sup.film                                                                 1634                                                                          cm.sup.-1             26 " "           "                                                                                   ##STR26##    "        2(COOH).sub.2                                                                            153.5-155             27 " "           "    (CH.sub.2).sub.2OPh                                                                         "        HCl        158-160               28 " "           "                                                                                   ##STR27##    "        "          140-142               29 " "           "    (CH.sub.2).sub.3Ph                                                                          "        --         oily product                                                                  ν.sup.film                                                                 1639                                                                          cm.sup.-1             30 " "           "    (CH.sub.2).sub.3N(CH.sub.3).sub.2                                                           "        2(COOH).sub.2                                                                            125-127               31 " "           "    (CH.sub.2).sub.3N(C.sub.2 H.sub.5).sub.2                                                    "        "          146.5-147.5           32 " "           "                                                                                   ##STR28##    "        --         oily product                                                                  ν.sup.film                                                                 1635 cm.sup.-1        33 " "           "                                                                                   ##STR29##    "        HCl        138-140               34 " "           "    CH.sub.3      CH ˜ CH.sub.3 *                                                                  --         oily product                                                                  ν.sup.film                                                                 1660                                                                          cm.sup.-1             35 " "           "    CH.sub.2 Ph   CH ˜ CH.sub.3 ***                                                                "          oily product                                                                  ν.sup. film                                                                1659                                                                          cm.sup.-1             36 " "           "                                                                                   ##STR30##    CH ˜ CH.sub.3 *                                                                  HCl        175-177               37 " "           "                                                                                   ##STR31##    CH ˜ CH.sub.3 **                                                                 "          185-187               38 " "           "                                                                                   ##STR32##    CH ˜ CH.sub.3 ***                                                                --         oily product                                                                  ν.sup.film                                                                 1658 cm.sup.-1        39 " "           "                                                                                   ##STR33##    CH ˜ CH.sub.3 ***                                                                HCl        156-158               40 " "           "    CH.sub.2 Ph   C(CH.sub.3).sub.2                                                                      --         oily product                                                                  ν.sup.film                                                                 1665                                                                          cm.sup.-1             41 " "           "                                                                                   ##STR34##    "        HCl        137-138               42 " "           "                                                                                   ##STR35##    "        --         62.5-64               43 " "           "                                                                                   ##STR36##    "        "          100-102               44 " "           "                                                                                   ##STR37##    "        "          100-101               45 " "           "                                                                                   ##STR38##    "        "          58-60                 46 " "           "    (CH.sub.2).sub.2OPh                                                                         "        "          76-78                 47 " "           "                                                                                   ##STR39##    "        "          oily product                                                                  ν.sup.film                                                                 1670 cm.sup.-1        48 1 4-Cl        "    CH.sub.3      CH.sub.2 HCl . 1/2H.sub.2 O                                                                       193-196               49 " "           "                                                                                   ##STR40##    "        --         132-133               50 " "           "    (CH.sub.2).sub.3N(CH.sub.3).sub.2                                                           "        2(COOH).sub.2                                                                            142-143.5             51 " 5-Cl        "                                                                                   ##STR41##    H    Ph  --         115-116               52 " "           "    CH.sub.2 Ph   Ph   Im  --         166.5-167             53 " "           "                                                                                   ##STR42##    "    "   --         187-188               54 " "           "                                                                                   ##STR43##    "    "   --         189-191               55 " "           "                                                                                   ##STR44##    "    "   --         165-167               56 " "           "                                                                                   ##STR45##    "    "   --         172-173.5             57 " "           "    CH.sub.2 Ph   CH.sub.2 HCl . 1/10H.sub.2 O                                                                      174-175               58 " "           "                                                                                   ##STR46##    "        "          188-190               59 " "           "                                                                                   ##STR47##    "        HCl . H.sub.2 O                                                                          172-174               60 " "           "                                                                                   ##STR48##    "        HCl        165-172               61 " "           "    CH.sub.3      "        "          239                   62 " "           "    n-C.sub.3 H.sub.7                                                                           "        "          178-181               63 " "           "    CH.sub.2 Ph   CH ˜ CH.sub.3 ***                                                                "          132-134               64 " "           "                                                                                   ##STR49##    "        "          211-212               65 " "           "                                                                                   ##STR50##    "        "          170-174               66 " "           "    CH.sub.2 Ph   C(CH.sub.3).sub.2                                                                      "          192-193.5             67 " "           "                                                                                   ##STR51##    "        "          201-203               68 " "           "                                                                                   ##STR52##    "        "          193-194               69 " "           "                                                                                   ##STR53##    "        --         106-108               70 " "           "                                                                                   ##STR54##    "        1/3H.sub.2 O                                                                             oily product                                                                  ν.sup.film                                                                 1668 cm.sup.-1        71 " "           "    CH.sub.3      CH ˜ Ph                                                                          --         118-118.5             72 " "           "    CH.sub.2 Ph   CH ˜ C.sub.2 H.sub.5 ***                                                         --         158.5-159.5           73 " "           "                                                                                   ##STR55##    "        HCl        220-222               74 " "           "                                                                                   ##STR56##    "        HCl        166-167               75 " "           "    (CH.sub.2).sub.3N(CH.sub.3).sub.2                                                           CH.sub.2 2(COOH).sub.2                                                                            105.5-107             76 "                                                                                ##STR57##  "                                                                                   ##STR58##    "        HCl        193-195               77 2 3,5-Cl      "    CH.sub.2 Ph   "        "          170-172               78 " "           "                                                                                   ##STR59##    "        "          155-165               79 " "           "                                                                                   ##STR60##    "        "          170-171               80 " "           "                                                                                   ##STR61##    "        "          150-153.5             81 " "           "                                                                                   ##STR62##    "        2(COOH).sub.2 . 1/3H.sub.2                                                               153-154               82 " "           "    (CH.sub.2).sub.3N(CH.sub.3).sub.2                                                           "        2(COOH).sub.2                                                                            119-120               83 0 --          3-O                                                                                 ##STR63##    "        1/2H.sub.2 O                                                                             oily product                                                                  ν.sup.film :                                                               1638 cm.sup.-1        84 " "            2-NH                                                                                "           CH.sub.3                                                                           Im  --         143.5-144             85 " "           "      "           CH.sub.2 "          147-148               86 " "                                                                                          ##STR64##                                                                           "           "        "          101-101.5             87 1 5-Cl        2-O  (CH.sub.2).sub.3N(CH.sub.3).sub.2                                                           C(CH.sub.3).sub.2                                                                      2(COOH).sub.2 . CH.sub.3                                                                 101-104               88                                                                                ##STR65##    "                                                                                   ##STR66##    H    H   HCl        166-167               89                                                                                ##STR67##    "      "           "    "   --         154-156               90                                                                                ##STR68##    "      "           "    "   "          142-143               91 "             "      "           CH.sub.2 --         120-121               __________________________________________________________________________     (Note)-                                                                       The meanings of abbreviations are as                                          Ph = phenyl                                                                   Im = imidazolyl                                                               i-Pr = isopropyl                                                              Tr = trifluoroacetyl                                                          *means that methyl (ethyl, phenyl) group takes cisform to imidazolyl          group.                                                                        **means that methyl (ethyl, phenyl) group takes transform to imidazolyl       group.                                                                        ***means the mixture of cis and transform.                               

REFERENCE EXAMPLE 1 ##STR69##

Compound (2) (500 mg) is hydrogenated in 14% hydrochloric acid-methanol(5 ml) in the presence of platinum oxide in a hydrogen stream. After theabsorption of 1 mole of hydrogen, the reaction is stopped. The reactionis filtered and the filtrate is concentrated. The residue is mixed withaqueous sodium hydrogencarbonate solution and extracted with methylenechloride. The organic layer is washed with water, dried over Glauber'ssalt and concentrated. The residue is crystallized from ethylacetate-isopropyl ether to give Compound (7) (456 mg). mp. 170.5°˜172°C.

REFERENCE EXAMPLE 2 ##STR70##

To a solution of N,N'-thionyldiimidazole prepared from imidazole (4.12g), thionyl chloride (1.8 g), and dry methylene chloride (20 ml) isadded Compound (1) (2 g), and the mixture is allowed to stand at roomtemperature overnight. The reaction mixture is mixed with ice-water andextracted with methylene chloride. The organic layer is washed withwater, dried, and concentrated. The residue is washed with ethylacetate-ether to give Compound (9) (2.72 g).

mp. 183°˜193° C.

Hydrochloride of Compound (9) (2HCl.H₂ O)

mp. 124°˜127° C.

The preparation for fungicides are as follows:

Preparation 1

A mixture of Compound (3) hydrochloride prepared in Example 1 (5 weightparts), clay (85 weight parts), and talc (10 weight parts) is pulverizedand formulated into a dust.

Preparation 2

A mixture of a compound prepared in Example 8 (50 weight parts),diatomaceous earth (45 weight parts), and calcium alkylbenzenesulfonate(2.5 weight parts) is pulverized, admixed, and formulated into awettable powder.

Preparation 3

A mixture of the compound prepared in Example 27 (30 weight parts),xylene (60 weight parts), and polyoxyethylene alkyl aryl ether (10weight parts) is admixed and formulated into an emulsion.

Preparation 4

A mixture of the compound prepared in Example 3 (5 weight parts), clay(85 weight parts), and talc (10 weight parts) is pulverized andformulated into a dust.

Preparation 5

A mixture of the compound prepared in Example 48 (50 weight parts),diatomaceous earth (45 weight parts), and calcium alkylbenzenesulfonate(2.5 weight parts) is pulverized, admixed, and formulated into awettable powder.

Preparation 6

A mixture of the compound prepared in Example 7 (30 weight parts),xylene (60 weight parts), and polyoxyethylene alkyl aryl ether (10weight parts) is admixed and formulated into an emulsion.

Preparation 7

The compound prepared in Example 62 (10 weight parts) is dissolved inwater (90 weight parts) to give a solution.

The preparations for antimycotics are as follows:

Preparation 8

    ______________________________________                                        Cream: The compound prepareed in Example 13                                                                    10 g                                                Bees wax                  100 g                                               Cetyl alcohol             50 g                                                2-Octyldodecanol          50 g                                                Propylene glycol          300 g                                               Mixture (1:1 w/w) of sorbitan mono-                                           stearate and polyoxyethylene sorbitan                                                                   50 g                                                monostearate                                                                  Mixture (1.9:0.2 w/w) of butyl paraben                                        and methyl paraben        2 g                                                 Mixture (0.06:1.25:9 w/w/w) of phosphoric                                     acid, sodium hydroxide and monosodium                                                                   10 g                                                phosphate dihydrate                                                           Distilled water           428 g                                                                         1000 g                                       ______________________________________                                    

Preparation 9

    ______________________________________                                        Gel:   Nitrate of the compound prepared in                                           Example 13              10 g                                                  Carbopol 940 (carboxyvinyl polymer)                                                                   15 g                                                  Ethanol                 100 g                                                 Propylene glycol        650 g                                                 Triisopropanolamine     10 g                                                  Distilled water         215 g                                                                         1000 g                                         ______________________________________                                    

What we claim is:
 1. A compound of the formula: ##STR71## wherein X ishalogen, nitro, C₁ to C₅ alkyl, C₁ to C₅ alkoxy or halobenzyloxy;m is aninteger of 0 to 3; Y is oxa, thia or imino optionally substituted by C₁to C₅ alkanoyl, C₁ to C₅ halo-alkanoyl or C₁ to C₅ alkyl; R¹ is C₁ to C₅alkyl, C₃ to C₁₀ dialkylaminoalkyl, C₁₅ to C₂₀ dibenzylamino-alkyl,1-pyrrolidinyl, 2-imidazolin-2-yl or a group of the formula --(CH₂)_(n)--Z--Q wherein n is an integer of 0 to 4, Z is oxa, thia or a singlebond and Q is phenyl or thienyl optionally substituted by 1 to 3 membersselected from the group consisting of halogen, nitro, C₁ to C₅ alkyl andC₁ to C₅ alkoxy; and R⁴ is C₁ to C₅ alkylidene optionally substituted byphenyl,the benzene ring in the above formula being optionally condensedwith another benzene ring, or a pharmaceutically acceptable acidaddition salt thereof.
 2. A compound according to claim 1, wherein R⁴ isCH₂.
 3. The compound 1-[1-(2-(3-chlorobenzyloxy)phenyl)vinyl]imidazole.4. The compound 1-[1-(2-(4-chlorobenzyloxy)phenyl)vinyl]imidazole. 5.The compound 1-[1-(2-(phenethyloxy)phenyl)vinyl]imidazole.
 6. Thecompound1-[2-(4-chlorobenzyloxy)phenyl]-1,1-bis(1-imidazolyl)-1-phenylmethane.